RATIONALE: Belinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving belinostat together with bortezomib may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving belinostat together with bortezomib in treating patients with relapsed or refractory acute leukemia or myelodysplastic syndrome.

Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: bortezomib

Given IV

Other Names:

LDP 341

MLN341

PS-341

VELCADE

Drug: belinostat

Given IV

Other Name: PXD101

Other: laboratory biomarker analysis

Correlative studies

Other Name: sample collection

Genetic: western blotting

Correlative studies

Other Names:

Blotting, Western

Western Blot

Other: pharmacological study

Correlative studies

Other Name: pharmacological studies

Other: flow cytometry

Correlative studies

Other Name: sample analysis

Detailed Description:

PRIMARY OBJECTIVES: I. To determine the recommended phase II doses for the combination of bortezomib and belinostat in patients with relapsed or refractory acute leukemia (AL), myelodysplasia (MDS), and chronic myelogenous leukemia in blast crisis. SECONDARY OBJECTIVES: I. Determine safety and tolerance and describe the toxicities of the combination. II. To demonstrate adequate methods for the assessment of pharmacodynamic response of leukemia cells from the bone marrow and/or peripheral blood in terms of effects on NF-kB (nuclear RelA by immunofluorescence microscopy), NF-kB dependent proteins XIAP and Bcl-xL, and BIM, and document pharmacodynamic responses observed in the course of this study. III. To document activity of the combination observed in the course of this study. OUTLINE: Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion

Relapsed or refractory acute leukemia

acute myeloid leukemia (AML) other than APL

acute lymphocytic leukemia (ALL)

acute leukemia that has evolved from a prior myelodysplastic syndrome - no requirement for prior therapy

Prior allogeneic stem cell transplant is allowed provided that >/= 12 months have elapsed since allogeneic transplant; no graft versus host disease is present; not currently on immunosuppressive therapy

AST, ALT =< 2.5 x upper limit of normal (ULN)

Female subject who is post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., oral or injectable hormonal methods; barrier methods such as intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study

Male subject agrees to use an acceptable method for contraception for the duration of the study

• History of resuscitated cardiac arrest. Note: persons without pre-existing cardiovascular comorbidities who have experienced resuscitated cardiac arrest in the setting of sepsis ARE eligible provided they have no residual cardiac abnormalities and providing they do not require ongoing medication to manage cardiac issues as an outcome of such an event.

Conduction abnormality or concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia

Known congenital long QT syndrome

Clinically significant infection including infection with HIV, or active hepatitis B or C

Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy

Planned ongoing treatment with other drugs thought to potentially adversely interact with belinostat

Strong or moderate CYP3A4 inhibitors

Patient has received other investigational drugs within 14 days before enrollment

If steroids for cancer control have been used, patients must be off these agents for >/= 1 week before starting treatment. Exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose < 10 mg/day is permitted.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01075425